Bovine fibrinogen methylated with thetrimethyl oxonium ion resulted in the polymerization of the fibrinogen. In 10 min the extent of modification was 18 carboxyl groups esterified with a 705 degree of polymerization. The methylated fibrinogen was totally polymerized in 30 min with approximately 100 carboxyl groups modified. The rate of aggregation was maximum in 5 to 10 min of reaction time with 12 carboxyl groups methylated. After 10 min the rate of aggregation decreased rapidly; however, some 80 carboxyl groups continued to be modified. The location of the critical groups methylated leading to the polymerization of the fibrinogen was evaluated and a minimum of three carboxylic acid residue were esterified in the N-terminal segment of fibrinopeptide-A in the structure of fibrinogen. These results implicate the methylation of carboxylic acid groups in the structure of fibrinopeptide-A as generating the polymerization. The esterification of fibrin polymer through methylation disrupts the appearance of periodic fibers in the formation of the fibrin network. Reptilase releases fibrinopeptide-A at a faster rate from canine citraconylated fibrinogen than from the native fibrinogen.